The purpose of this study is to investigate the enzymes and factors necessary for the activation of human plasma prekallikrein. Studies of the mechanism by which this enzyme is activated in human blood have clearly shown a relationship between the kallikrein-kinin system, the coagulation system and the plasminogen-plasmin system. The current data classifies human plasma kallikrein and its preferred substrate in plasma, high molecular weight kininogen, as two of intrinsic clotting factors and suggests that an unidentified factor (Factor W) is required for the full activation of Hageman factor and thus to initiate clotting, plasminogen activation and platelet aggregation.